title: Attenuation of lung ischemia-reperfusion injury by rho-associated kinase inhibition in a rat model of lung transplantation.
abstract: BACKGROUND
  A signaling pathway of the small GTPase Rho and Rho-associated coiled-coil-forming protein kinase (ROCK), regulates the contraction of endothelial cells. We studied the effects of Y-27632, a specific ROCK inhibitor, to clarify the role of Rho/ROCK in the pathogenesis of ischemia-reperfusion lung injury in a rat model of single-lung transplantation (LTX).
  
  
  METHODS
  We flushed 5 donor rat lungs with Euro-Collins solution, and 5 donor lungs with Euro-Collins + Y-27632, 0.03 mg/ml, and preserved the lungs for 6 h at 4°C before reperfusion for 4 h. The 5 rat recipients of Y-27632-treated lungs also received a 10-mg/kg bolus of Y-27632 i.p. 30 min before reperfusion.
  
  
  RESULTS
  Pretreatment of the donor lungs and recipient rats with Y-27632 prominently suppressed the post-LTX edema, while the permeability index was only slightly decreased. The (1) numbers of neutrophils and macrophages, and (2) tumor necrosis factor (TNF)-α concentration, were significantly lower in the bronchoalveolar lavage fluid of treated than untreated lungs.
  
  
  CONCLUSIONS
  Y-27632 (1) inhibited the migration of inflammatory cells into the alveolar space, (2) decreased the production of TNF-α, and (3) attenuated the edema after LTX. Endothelial Rho and ROCK may play an important role in the pathogenesis of post-LTX injury.
authors.affiliation: Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Mitsutomo
authors.initials: M
authors.lastname: Kohno
authors.forename: Masazumi
authors.initials: M
authors.lastname: Watanabe
authors.forename: Taichiro
authors.initials: T
authors.lastname: Goto
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kamiyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohtsuka
authors.forename: Sadatomo
authors.initials: S
authors.lastname: Tasaka
authors.forename: Makoto
authors.initials: M
authors.lastname: Sawafuji
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002633:Chemotaxis / Q000187:drug effects; D019610:Cytoprotection; D004195:Disease Models, Animal; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D055370:Lung Injury / Q000201:enzymology / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D016040:Lung Transplantation / Q000009:adverse effects*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D020556:Neutrophil Infiltration / Q000187:drug effects; D010539:Permeability; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000201:enzymology / Q000517:prevention & control; D011725:Pyridines / Q000494:pharmacology*; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000201:enzymology / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000577:Amides; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; C108830:Y 27632; D054460:rho-Associated Kinases